Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
Conditions
Keywords
primary myelofibrosis, secondary myelofibrosis, essential thrombocythemia, polycythemia vera
Brief summary
RATIONALE: Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying the side effects and how well low-dose decitabine works in treating patients with symptomatic myelofibrosis.
Detailed description
OBJECTIVES: * Determine the efficacy and safety of low-dose decitabine in patients with symptomatic primary myelofibrosis (PMF) or post essential thrombocythemic (ET) or polycythemic vera (PV) myelofibrosis. * Analyze the ability of this drug to decrease pathologic angiogenesis and other stromal reactive features intrinsic to PMF or post ET/PV myelofibrosis. OUTLINE: Patients receive low-dose decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving partial remission, complete remission, or clinical improvement may receive up to 12 courses of decitabine in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for up to 3 years.
Interventions
DRUGDacogen
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histological confirmation of primary myelofibrosis or post essential thrombocythemic or polycythemic vera myelofibrosis * Reticulin fibrosis ≥ grade 1 * Evaluable and symptomatic disease worthy of treatment, characterized by ≥ 1 of the following: * Anemia, defined as hemoglobin \< 11 g/dL or erythrocyte transfusion dependence * Palpable and symptomatic splenomegaly (palpable and symptomatic hepatomegaly is acceptable if previously splenectomized) * Severe, disease-related constitutional symptoms, including ≥ 1 of the following: * Severe night sweats * Fevers * Weight loss * Bone pain * Absence of t(9;22) by fluorescent in situ hybridization (FISH) or standard cytogenetics OR prior demonstration of a lack of this translocation PATIENT CHARACTERISTICS: * Eastern Co-operative Oncology Group (ECOG) performance status 0-3 * Absolute neutrophil count (ANC) ≥ 1,000/mm³ * Platelet count ≥ 50,000/mm³ * Creatinine ≤ 2.0 mg/dL * Direct or total bilirubin ≤ 2.0 mg/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN if elevation is attributed to hepatic extramedullary hematopoiesis) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Not incarcerated in a municipality, county, state, or federal prison * No serious medical condition or psychiatric illness that would preclude signing the informed consent * No condition that, in the opinion of the treating physician, places the patient at unacceptable risk for study participation or confounds the ability to interpret study data * Able to adhere to the study visit schedule and other study requirements PRIOR CONCURRENT THERAPY: * No other concurrent chemotherapy (e.g., hydroxyurea, thalidomide, interferon alpha, anagrelide, or other myelosuppressive agent) or experimental therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve a Confirmed Response (Complete Remission (CR), Partial Remission (PR), or Clinical Improvement (CI)), According to International Working Group (IWG) Consensus Criteria. | Every 4 weeks during treatment (up to 16 weeks) | Confirmed response: objective status of CR, PR, or CI on 2 consecutive evaluations \>=4 weeks apart. CR:Complete resolution of disease-related symptoms and signs; peripheral blood count remission; normal leukocyte differential; bone marrow histologic remission. PR: All criteria for CR except the bone marrow histologic remission. CI: one of the following in the absence of both disease progression and CR/PR: minimum (MI) 20-g/L increase (INC) in hemoglobin level; MI 50% reduction in palpable splenomegaly (\>=10cm); MI 100% INC in platelet count(\>=50000x10\^9/L) or ANC (\>=0.5x10\^9/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival(OS) | up to 3 years | OS was defined as the time from registration to death of any cause. |
| Time to Disease Progression | up to 3 years | Time to disease progression is defined as the time from registration to progression of disease or death due to any cause. Progression was defined as any one or more of the following: 1)progressive splenomegaly; 2) leukemic transformation confirmed by a bone marrow blast count of \>= 20%; 3) an increase in peripheral blood blast percentage of \>=20% that lasts for \>= 8 weeks. |
| Number of Participants With Constitutional Symptoms | Up to 48 weeks | Constitutional symptoms including the presence of one or more of the following felt to be attributed to the disease: severe night sweats, fevers, weight loss and bone pain. Symptoms were assessed every cycle during treatment. |
| Number of Participants With Severe Adverse Events | Up to 48 weeks | Severe adverse events were defined as grade 3 or higher, regardless of attribution to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Adverse events were assessed every cycle during treatment. |
Countries
United States
Participant flow
Recruitment details
Four (4) patient was recruited from March 2008 to May 2009 at Mayo Clinic. This trial was permanently closed in September 2009 due to slow accrual.
Participants by arm
| Arm | Count |
|---|---|
| Decitabine 20 mg/m\^2/day intravenous over one hour on days 1-5 out of 28 days of treatment cycle | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Disease Progression | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Other | 1 |
Baseline characteristics
| Characteristic | Decitabine |
|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 6.6 |
| Category of Primary myelofibrosis Post Essential Thrombocythemia (ET) Myelofibrosis | 1 participants |
| Category of Primary myelofibrosis Post Polycythemia Vera (PV) Myelofibrosis | 1 participants |
| Category of Primary myelofibrosis Primary Myelofibrosis | 2 participants |
| Prior bleeding events felt to be related to underlying disease No | 4 participants |
| Prior bleeding events felt to be related to underlying disease Yes | 0 participants |
| Prior disease specific therapy (including drugs, stem cell transplant, or splenectomy) No | 2 participants |
| Prior disease specific therapy (including drugs, stem cell transplant, or splenectomy) Yes | 2 participants |
| Prior thrombosis No | 2 participants |
| Prior thrombosis Yes | 2 participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Number of Participants Who Achieve a Confirmed Response (Complete Remission (CR), Partial Remission (PR), or Clinical Improvement (CI)), According to International Working Group (IWG) Consensus Criteria.
Confirmed response: objective status of CR, PR, or CI on 2 consecutive evaluations \>=4 weeks apart. CR:Complete resolution of disease-related symptoms and signs; peripheral blood count remission; normal leukocyte differential; bone marrow histologic remission. PR: All criteria for CR except the bone marrow histologic remission. CI: one of the following in the absence of both disease progression and CR/PR: minimum (MI) 20-g/L increase (INC) in hemoglobin level; MI 50% reduction in palpable splenomegaly (\>=10cm); MI 100% INC in platelet count(\>=50000x10\^9/L) or ANC (\>=0.5x10\^9/L)
Time frame: Every 4 weeks during treatment (up to 16 weeks)
Population: All participants who met the eligibility criteria that have signed a consent form and went on treatment were evaluable for response. The study was terminated early due to slow enrollment. The primary outcome measure should be assessed with caution.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Decitabine | Number of Participants Who Achieve a Confirmed Response (Complete Remission (CR), Partial Remission (PR), or Clinical Improvement (CI)), According to International Working Group (IWG) Consensus Criteria. | 1 participants |
Secondary
Number of Participants With Constitutional Symptoms
Constitutional symptoms including the presence of one or more of the following felt to be attributed to the disease: severe night sweats, fevers, weight loss and bone pain. Symptoms were assessed every cycle during treatment.
Time frame: Up to 48 weeks
Population: Study terminated prematurely. Analysis not performed.
Secondary
Number of Participants With Severe Adverse Events
Severe adverse events were defined as grade 3 or higher, regardless of attribution to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Adverse events were assessed every cycle during treatment.
Time frame: Up to 48 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Decitabine | Number of Participants With Severe Adverse Events | Anemia | 3 participants |
| Decitabine | Number of Participants With Severe Adverse Events | Platelet count decreased | 1 participants |
| Decitabine | Number of Participants With Severe Adverse Events | Neutrophil count decreased | 2 participants |
| Decitabine | Number of Participants With Severe Adverse Events | Leukopenia | 1 participants |
| Decitabine | Number of Participants With Severe Adverse Events | Alkaline Phosphatase Increased | 1 participants |
| Decitabine | Number of Participants With Severe Adverse Events | Ascites | 1 participants |
| Decitabine | Number of Participants With Severe Adverse Events | Clostridial Infection | 1 participants |
| Decitabine | Number of Participants With Severe Adverse Events | Hyperglycemia | 1 participants |
Secondary
Overall Survival(OS)
OS was defined as the time from registration to death of any cause.
Time frame: up to 3 years
Population: Study terminated prematurely. Analysis not performed.
Secondary
Time to Disease Progression
Time to disease progression is defined as the time from registration to progression of disease or death due to any cause. Progression was defined as any one or more of the following: 1)progressive splenomegaly; 2) leukemic transformation confirmed by a bone marrow blast count of \>= 20%; 3) an increase in peripheral blood blast percentage of \>=20% that lasts for \>= 8 weeks.
Time frame: up to 3 years
Population: Study terminated prematurely. Analysis not performed.